Mosquitoes are a world-wide nuisance and health hazard to humans and other animals. As currently no efficient means exists for the eradication of the mosquito, the identification of new strategies for mosquito control are clearly dependent on a better understanding of the biochemical and genetic basis for mosquito development and transmission of mosquito-borne diseases. In holometabolous insects such as the mosquito, hexameric serum proteins or hexamerins are abundantly synthesized during the last stage of larval development and are believed to serve primarily as a storage form of amino acids for use during non-feeding stages. We have undertaken a study of mosquito hexamerins in order to examine how regulated expression and utilization of these proteins during adult development may affect different physiological states in this blood-feeding disease vector. Recently, we characterized the structure and developmentally regulated appearance of hexamerins in the larval, pupal and adult hemolymph of two well- studied mosquitoes, Aedes aegypti and Anopheles gambiae. The major protein in both species is a heterohexamer composed of two types of subunits which share some features with higher dipteran homologues. Furthermore, accumulation of mosquito hexamerin mRNA is clearly developmentally regulated. We propose to continue the study of mosquito hexamerins, focusing on the basis for regulated hexamerin gene activity and potential roles for hexamerins during adult development. Regulatory DNA sequences underlying tissue-, stage-, and hormone-specific expression will be mapped using gene transfer in Drosophila and Aedes. Specific uptake, storage and/or utilization by reproductive tissues, the cuticle, blood cells or the fat body will be examined. Possible receptor-mediated uptake will characterized and will serve as the basis for isolation of clones for a putative receptor gene. The effect of specific hexamerin synthesis and accumulation in larvae on the onset of vitellogenesis will-be studied by comparing blood-feeding and non- blood-feeding mosquitoes. This study should provide a better understanding of hexamerin expression and function during mosquito development and contribute valuable molecular and biochemical tools for developing new strategies to control and genetically manipulate the mosquito as a disease vector.